SUMOylation of GPS2 protein regulates its transcription-suppressing function.
SUMOylation of GPS2 protein regulates its transcription-suppressing function.
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GPS2 蛋白的 SUMO 化调节其转录抑制功能
DOI：
10.1091/mbc.e13-12-0733
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发表时间：
2014-08-15
影响因子：
3.3
通讯作者：
Wu H
中科院分区：
文献类型：
--
作者：
Bi H;Li S;Wang M;Jia Z;Chang AK;Pang P;Wu H
GPS 2可以被SUMO-1修饰。SUMO化可稳定GPS 2蛋白并增强其抑制转录的能力，以及通过增加其与SMRT的结合来促进其抑制ERα介导的转录的能力，如在MCF-7和T47 D细胞中所证明的。G蛋白通路抑制因子2（GPS 2）是G蛋白活化的丝裂原活化蛋白激酶信号传导的人类抑制因子。它参与许多生理过程，包括DNA修复、细胞增殖、凋亡和脑发育。在这项研究中，我们发现GPS 2可以被小泛素样修饰物（SUMO）SUMO-1修饰，而不是SUMO-2或-3。两个SUMO化位点（K45和K71）被确定在GPS 2的N-末端卷曲螺旋结构域。用精氨酸取代K45减少SUMO化，而用精氨酸取代K71或K45和K71两者废除SUMO化，与野生型和两个单突变体GPS 2相比，更多的双突变体GPS 2出现在胞质溶胶中而不是细胞核中。SUMO化通过促进GPS 2与TBL 1的相互作用并减少其泛素化来稳定GPS 2蛋白。SUMO化还增强了GPS 2抑制转录的能力，并通过增加其与SMRT的结合来促进其抑制雌激素受体α介导的转录的能力，如在MCF-7和T47 D细胞中所证明的。此外，GPS 2的SUMO化还抑制MCF-7和T47 D细胞的增殖。这些结果表明，翻译后修饰的GPS 2的SUMO化可能是一个关键因素，调节GPS 2的功能在体内。
GPS2 can be modified by SUMO-1. SUMOylation stabilizes GPS2 protein and enhances its ability to suppress transcription, as well as promoting its ability to inhibit ERα-mediated transcription by increasing its association with SMRT, as demonstrated in MCF-7 and T47D cells. G-protein pathway suppressor 2 (GPS2) is a human suppressor of G protein–activated mitogen-activated protein kinase signaling. It is involved in many physiological processes, including DNA repair, cell proliferation, apoptosis, and brain development. In this study, we show that GPS2 can be modified by the small ubiquitin-like modifier (SUMO) SUMO-1 but not SUMO-2 or -3. Two SUMOylation sites (K45 and K71) are identified in the N-terminal coiled-coil domain of GPS2. Substitution of K45 with arginine reduces SUMOylation, whereas substitution of K71 or both K45 and K71 with arginine abolishes SUMOylation, with more of the double mutant GPS2 appearing in the cytosol than in the nucleus compared with wild type and the two-single-mutant GPS2. SUMOylation stabilizes GPS2 protein by promoting its interaction with TBL1 and reducing its ubiquitination. SUMOylation also enhances the ability of GPS2 to suppress transcription and promotes its ability to inhibit estrogen receptor α–mediated transcription by increasing its association with SMRT, as demonstrated in MCF-7 and T47D cells. Moreover, SUMOylation of GPS2 also represses the proliferation of MCF-7 and T47D cells. These findings suggest that posttranslational modification of GPS2 by SUMOylation may serve as a key factor that regulates the function of GPS2 in vivo.